Int. J. Pharm. Sci. Rev. Res., 36(2), January – February 2016; Article No. 16, Pages: 90-98
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Review Article
Nanoparticles: A Novel Avenue in Cancer Therapy
Deeksha tripathi*, Rajeshwar Kamal Kant Arya, Mridula Pant
Department of Pharmaceutical Sciences, Bhimtal Campus, Kumaun University Block Road, Bhimtal, Nainital, India.
*Corresponding author’s E-mail: tripathi.deeksha.90@gmail.com
Accepted on: 23-12-2015; Finalized on: 31-01-2016.
ABSTRACT
Cancer is a major health concern in the world. Chemotherapy is widely used to treat cancer either alone or in combination with
other therapy. Chemotherapy is associated with several problems such as lack of specificity, poor aqueous solubility and multidrug
resistance. Nanotechnology has emerged as promising approach to treat cancer effectively. Nanotechnology based nanoparticles
have shown great potential in overcoming limitations of conventional chemotherapy. Nanoparticles have several properties such as
tunable size and required surface characteristics which make them ideal candidate for drug targeting. Several types of nanoparticles
are engineered to target tumor sites without causing any harm to normal cells. Major advantage of drug loaded nanoparticles is,
they reach to tumor sites with minimal loss and affect only defected cell without any harm to normal cells. Nanoparticles
accumulate specifically to desired cell either by passive or ligand based target mechanism. Some nanoformulations have approved
and some are under clinical trials. This review discusses different types of nanoparticles along with targeting strategies. It also
discusses the potential of nanoparticles in cancer diagnosis and treatment.
Keywords: Nanoparticles, nanotechnology, tumor imaging, photodynamic therapy, photothermal therapy, theranostic agent.
INTRODUCTION
C
ancer is a disease characterized by uncontrolled
proliferation of cells. Cancer is one of the major
health concerns which affect millions of people.
There are over 100 types of cancer and each is classified
by the organs or tissues where the cancers form1.
According to World Cancer Report 14 million new cases of
cancer with 8.2 million cancer related deaths (in 2012)
are reported2. Treatment of cancer includes surgical
removal, radiation, chemotherapy and hormone therapy3.
Chemotherapy is a first line treatment in almost all types
of cancer. However, it accompanies with a major problem
lack of selective toxicity, results in the damage of normal
healthy cells which will narrow down therapeutic index,
1
and thereby results in side effects and poor outcome .
Treatment of cancer lacks selective delivery of
systemically administered chemotherapeutic agents, poor
solubility and distribution, unfavorable pharmacokinetics
4
and high-tissue damage or toxicity . It reported that
amount of drug accumulated in normal viscera is 10-20
fold higher than that in the same weight of tumor site and
many anticancer drugs are not able to penetrate more
than 40-50 mm (equitable to combined diameter of 3-5
1
cells) from the vasculature . To circumvent such
obstacles, it has become important to develop novel and
5
effective ways to remove cancer cells .
Nanotechnology has emerged as a promising approach in
cancer treatment. Nanotechnology is a technology
performed on nano-scale (size range from 1nm to 1000
6
nm) .
Nanomedicines are utilized to overcome the several
3
limitations of conventional drug delivery system .
Nanoparticles have unique physical and chemical
properties which provide them better access to tumor
sites. Nano size and tunable surface properties make
Nanoparticles suitable for cancer treatment7.
In this review we will briefly discuss the local drug
delivery systems by means of various nanoparticles which
serve as an appropriate platform in the treatment of
cancer.
Nanoparticle Properties
Nanoparticles have shown potential in overcoming
various challenges of conventional cancer therapy. Major
disadvantages of conventional chemotherapy are nonspecificity and toxicity.
Size
Nanoparticles have tunable size. Nano-carriers are large
enough to prevent their rapid leakage into blood
capillaries but small enough to escape by macrophages
capture that are lodged in reticuloendothelial cell. The
size of the sinusoid in the spleen and fenestra of the
8
Kuffer cells in the liver varies from 150 to 200 nm and
the size of gap junction between endothelial cells of the
9
leaky tumor vasculature may vary from 100 to 600 nm .
The maximum size of nanoparticles allowing penetration
10
through cell membranes is known to be 500 nm . Long
term circulation is important for targeted delivery and
sustained release. Particle size is known to be intrinsically
related to the rate of clearance from the blood
10
circulation .
Surface Characteristics
Surface characteristics also determine the life span of
nanoparticles during circulation in blood. Nanoparticles
should have hydrophilic surface to avoid macrophage
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Int. J. Pharm. Sci. Rev. Res., 36(2), January – February 2016; Article No. 16, Pages: 90-98
capture11. This can be achieved either by coating of
nanoparticles with hydrophilic polymers or by forming
block copolymers with hydrophilic and hydrophobic
10
domain . Additionally, tumor cells bear relatively high
negative surface charge than normal cells. Cationic
nanoparticles bind with negatively charged phospholipids
head groups preferentially expressed on tumor
endothelial cells. Cytotoxicity potential of polymeric
nanoparticles largely depends on cell internalization and
sub-cellular localization of the nanoparticles which is
governed by nature of polymeric surface charge. Cationic
nanoparticles have been found to sensitize the cancer
cells to effects of paclitaxel for improved anticancer
activity12.
Challenges overcome by Targeted Nanoparticles in
Cancer Treatment
Various problems such as poor aqueous solubility, high
systemic toxicity, lack of specificity to target site
associated with conventional chemotherapy can be
overcome by targeted nanoparticles. Additionally, some
cancer cells develop drug resistance over drug treatment
course. Targeted nanoparticles have shown potential to
overcome these limitations6,13,14.
Majority of chemotherapeutics are hydrophobic in nature
and unable to cross the aqueous environment (e.g., the
body and tissue fluids in vivo) surrounding a cell and then
penetrate the cell membrane to eventually reach
intracellular targets. Additionally, on intravenous
administration these drugs aggregate and cause local
toxicity. Encapsulation is an efficient approach to
overcome this limitation. Park and co-workers found that
nano-sized micelles based on amphiphilic block
copolymers could serve as a carrier for the delivery of
drugs poorly soluble in water (such as paclitaxel),
significantly increasing the drug concentration in an
aqueous medium by a factor of more than 100013.
Anti-cancer drugs distribute indiscriminately to normal
organs and tissues because of lack of tumor specificity.
Thus, cancer cells are exposed to a lower concentration of
the drug than normal cells, resulting in not only
decreased effectiveness but also increased toxicity15. The
functionalization of the nanoparticles helps to achieve
extended blood residence time, reduce nonspecific
distribution, and target tissues or specific cell surface
antigens with a targeting ligand (peptide, aptamer,
antibody/antibody fragment, small molecule)12. It is also
achieved by encapsulating drugs in nanoparticles such as
liposomes. PEGylated liposomal doxorubicin (with brand
names of Doxil in the US and Caelyx in Europe)16 has been
shown to significantly improve the therapeutic index of
doxorubicin both in preclinical and clinical studies17.
Drug resistance has emerged as a major obstacle limiting
the therapeutic efficacy of chemotherapeutic agents.
Among several mechanisms of drug resistance, Pglycoprotein is the best known and most extensively
investigated. It has been suggested that nanoparticles
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may be able to circumvent P-glycoprotein– mediated
resistance. One possible mechanism is that nanoparticles
may avoid recognition by the P-glycoprotein efflux pump
by means of being enveloped in an endosome when
entering the cell, leading to high intracellular drug
concentrations. Ligand-targeted strategies, especially
those using receptor-targeting ligands, may have
particular potential for overcoming drug resistance
because these ligands are usually internalized via
receptor-mediated endocytosis. Indeed, a folate
receptor–targeted, pH-sensitive polymeric micelle
containing doxorubicin and transferrin-conjugated
paclitaxel-loaded nanoparticles exhibited greater
inhibitory activity against drug-resistant MCF-7 cells
and/or xenografts than their nontargeted free drug
counterparts11.
Types of Nanoparticles used in Cancer Therapy
Polymer based Nanoparticles
Biodegradable polymers such as chitosan, gelatin and
collagen poly caprolactone or non biodegradable
polymers such as poly lactic acid (PLA) and poly Lactico
Glycolic acid (PLGA) are used to prepare colloidal solid
particles1. It is reported that polymeric nanoparticles have
more efficacy for targeted delivery of anticancer agent
such as paclitaxel18. Polymeric nanoparticles (figure 1)
possess unique physicochemical characteristics which
provide them higher stability, sharper size distribution,
sustained and more controllable drug-release profile and
higher loading capacity for poor water soluble drugs19.
For instance, Danhier prepared paclitaxel loaded PEGPLGA based nanoparticles grafted with RGD peptide and
found that these nanoparticles delayed tumor growth
more efficiently and prolonged survival time of mice
compared with non-targeted nanoparticles20.
Polymer Derived Nanoparticles
Micelles (figure 1) assembled with hydrophobic reservoir
as drug carrier and hydrophilic shell makes the particle an
ideal candidate for i.v. administration11. Paclitaxel loaded
micellar formulation consisting PEG and modified
polyaspartate NK105 was prepared. Preclinical studies in
mice had shown that reduced dose of NK105 had same
antitumor activity with high dose of free paclitaxel.
Additionally, NK105 have shown less hypersensitivity
reactions in patients suffering from pancreatic, bile duct,
gastric, and colonic cancers compared to systemic
paclitaxel treatment during the phase I trial21.
Lipid based Nanoparticles
Liposomes (figure 1) in the range of 30-100 nm are
formed with various phospholipids such as
phosphatidylcholine,
phosphatidylethanolamine,
phosphatidylglycerol and phosphatidylserine, and other
molecules such as cholesterol. Polyethylene glycol coated
liposomes have increased circulation time of liposome
from few hours to approximately 45 hours19. O. Brien
studied and found that PEGylated liposomal doxorubicin
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Int. J. Pharm. Sci. Rev. Res., 36(2), January – February 2016; Article No. 16, Pages: 90-98
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has prolonged circulation time which facilitate greater
uptake PLD liposomes in tumor tissues. Additionally, PLD
22
liposomes reduced drug delivery to normal tissues .
intratumoral concentration of gold using GNP-cetuximabgemcitabine nano-complex compared with untargeted
GNPs with minimal retention in liver or kidney26.
In the study Chang found that survival rate of mice and
bioavailability of doxorubicin was higher when treated
with novel peptide ligand coupled with liposomes
carrying doxorubicin15.
Radioactive properties of gold can be utilized for cancer
198
treatment. Chanda N. proposed that AuNPs will serve
as new generation of therapeutic agents with potential to
eliminate serious clinical impediments associated with
existing heterogeneous (seed-based) brachytherapy
agents for treatment of various types of human cancers.
Dendrimers
Dendrimers (figure 1) are synthetic polymers, unimolecular, mono-dispersible, multi-branched and three
dimensional structures with well defined molecular
weights with a size of 1-10 nm made up of
macromolecules such as poly (N-isopropylacrylamide)polystyrene and poly(ethylene oxide)-poly(-benzyl-Laspartate)18,1.
The structure of dendrimers involve initiator core, layers
of branched repeating units and functional end groups on
outer shell. Both water soluble and insoluble drug can be
given concurrently with the help of dendrimers19.
Lai prepared by conjugating doxorubicin to
polyamidoamine dendrimers with the help of pH sensitive
and insensitive linkers to improve efficacy and reduce
side effects of these drugs23.
Carbon Nanotubes
Carbon nanotubes (figure 1) are formed by rolling single
or multiple grapheme sheets to form cylinder18.
Carbon nanotubes are completely insoluble in all solvents
but chemical modification can render them to water
soluble and functionalized so that they can be linked to
wide variety of active molecules such as peptide, protein,
nucleic acid and therapeutic agents.
Methotrexate, an anticancer agent covalently linked to
carbon nanotubes with fluorescent agent11. There is lack
of toxicity results because no clinical trials are performed
using carbon nanotubes.
Gold Nanoparticles
Gold nanoparticles (GNPs) are used to detect tumors and
metastasis in many solid tumors6. Easy conjugation with
bio-molecules and high absorption efficiencies are the
two unique characteristics of gold nano-materials which
make them ideal candidate for therapeutic applications24.
GNPs (figure 1) are conjugated with tumor necrosis factor
(TNF) alpha which mainly accumulate in tumor sites and
therefore prevents the toxic effects of TNF on healthy
tissues.
Additionally, gold nanoparticles have been used to deliver
anticancer
therapeutic
agents.
For
instance,
Methotrexate is highly water soluble drug which results in
poor tumor retention but after conjugating with GNPs
tumor retention and therapeutic efficacy of drug
increases25. GNPs can be used targeted delivery of
chemotherapeutics.
Patra
demonstrated
high
Gum Arabic glycoprotein- 198AuNPs complex was
prepared. Intratumoral administration of this complex in
mice resulted in significant tumor regression and effective
control in tumor growth of prostrate over 30 days
without any harm to nontargeted organs28.
Magnetic Nanoparticles
Magnetic nanoparticles (figure 1) have been investigated
and studied in past few years. It was studied that oleic
acid coated iron oxide nanoparticles when embedded
with chemotherapeutics such as doxorubicin and
paclitaxel loading efficiency was increased up to 95%18.
Jurgons R. studied effects of magnetic nanoparticles and
chemotherapeutic agent complex in rabbits29.
Moreover, Kohler fabricated Methotrexate-magnetic
nanoparticles complex or Methotrexate- PEG-magnetic
nanoparticles complex to target folate receptor over
expressing cancer cells. This complex induces apoptosis in
cancer cells and minimizes toxicity of methotrexate to
normal cells24.
Quantum Dots
Due to unique physical properties quantum dots have
become area of intense research that can be utilized for
cancer. Quantum Dots(QD) (figure 1) are usually made up
of inorganic transition metal such as cadmium selenide
(CdSe), cadmium telluride (CdTe), indium phosphide (InP),
and indium arsenide (InAs) as a core elements inside a
shell of zinc sulfide (ZnS). Small size and ability to
conjugate with targeting molecule give them easy access
to systemic circulation and specific retention in tumor
7
sites . Bagalcote fabricated QD-Aptamer complex that
could deliver chemotherapeutic agent and sense drug
delivery simultaneously based on mechanism of
Fluorescence Resonance Energy Transfer24.
Nanodiamonds
Nanodiamonds (NDs) are used for targeted delivery.
Nanodiamonds were bound to doxorubicin and this
complex was encapsulated with polymer microfilm in
order to achieve sustained release of drug for period of 1
month18. NDs (figure 1) have emerged as unique nanocarrier due to their biocompatibility, scalable synthetic
methods and carbon surface which facilitate bio agent
attachment. ND attachment has shown to increase
imaging efficacy, sustain drug release, boost therapeutic
efficiency and improve drug safety profile in both cell
based and animal model18.
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Polymeric Nanoparticle
Polymeric Micelles
Dendrimer
Liposome
Magnetic Nanoparticle
Gold Nanoparticle
Nanodiamonds
Carbon Nanotubes
Quantum Dot
Figure 1: Types of Nanoparticles Used in Cancer Therapy
Examples of Nanomedicines for Cancer approved by FDA and those undergoing Clinical Trials
Following table represents some examples of nanoformulations which are either approved or under clinical
investigations.
Table-1 Examples of nanomedicines for cancer approved by FDA and those undergoing clinical trials30
Drug Product
Active Ingredient
Manufacturer
Indications
FDA Approved
Date/Clinical Trial State
Doxil(Caelyx)
PEGylated Doxorubicin
Orthobiotech, ScheringPlough
Ovarian/Breast Cancer
November 1995
Various Cancers
Jan 05
Metastatic Pancreatic
Cancer
September 2013
Albumin-bound paclitaxel
Nano-spheres
Abraxis Biosciences,
Astragenecea
Abraxane
Nab paclitaxel in
combination with
gemcitabine
Celegene
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Myocet
Liposome encapsulated
Doxorubicin
Elan
Pharmaceuticals/Sopherion
Therapeutics
Breast Cancer
2000 Approved in Europe
and Canada
DaunoXome
Liposome encapsulated
Daunorubicin
Gilead Science
HIV related Kaposi
sarcoma
Apr-96
DepoCyt
Liposomal Cytarabine
Skye Pharma, Enzon
Lymphomatous
meningitis
Apr 99
Oncaspar
PEGasparginase
Enzon
Acute Lymphocytic
leukemia
Feb 94
Onco- TCS
Liposomal Vincristine
Inex
Non-Hodgkin
Lymphoma
In clinical phase I/II
LEP-ETU
Liposomal Paclitaxel
Neopharma
Ovarian/Breast/lung
Cancers
In clinical phase I/II
Aroplatin
Liposomal Cisplatin
Analog
Antigenics Inc.
Colorectal Cancer
In clinical phase I/II
OSI-211
Liposomal Lurtotecan
OSI
Lung Cancer/Recurrent
Ovarian
In clinical phase II
SPI-77
Stealth Liposomal
Cisplatin
Alza
Head& Neck
Cancer/Lung Cancer
In clinical phase III
EndoTAG-I
Paclitaxel
Medigene, SynCore
Biotechnology
Breast Cancer,
Pancreatic Cancer
In clinical phase II
Aug 12
In clinical phase III
Marqibo
Vincristine
Talon Therapeutics
Philadelphia
Chromosome negative
Lymphoblastic
Leukemia
ThermoDox
Doxorubicin
Celsion Corporation
Hepatocellular
Carcinoma
Targeting Strategies of Nanoparticles in Cancer Therapy
Nanoparticles are designed to target desired cell by
various modifications such as changing in chemical and
physical properties3 and for a desired therapeutic effect
anticancer drug should be able to reach tumor sites
through the penetration of barriers in the body with
minimal loss of volume and activity during circulation. In
addition to this, after reaching tumor sites the drugs
should have ability to selectively kill tumor cells without
affecting normal cells11. Drug loaded nanoparticles reach
to tumor sites either by passive targeting or active
targeting. Drug loaded nanoparticle is represented in
figure 3.
ranges from 100 to 780nm. Nanoparticles of below this
size range easily pass through cells. Drug loaded
nanoparticles can be targeted to specific organ by passive
diffusion or convection and lack of lymphatic drainage
facilitates diffusion process. Loose lymphatic network and
leaky vasculature of tumor sites resist inward flow of
molecule which provides high retention time in tumor
3
interstitium . Liu had shown passive targeting of quantum
34
dot probe in leaky vasculature (figure 3) .
Passive Targeting
Passive targeting is based on the accumulation of dug
around regions of tumor with leaky vasculature known as
enhanced permeation and retention (EPR) effect31.
Defective vascular architecture induces an EPR and
permits accumulation of nanoparticles in the tumor
interstitial space (figure 2)6. Due to lack of apoptosis
cancerous cells proliferate abnormally and suck nutritious
agents through blood vessels forming leaky blood vessels
and these leaky blood vessels are also formed due to
basement membrane abnormalities and decreased
number of pericytes lining rapidly proliferating
endothelial cells. The pore size of leaky endothelial cells
Figure 2: Nanoparticles accumulation in tumor tissue
through EPR effect.
Active Targeting
Active targeting agents having selective affinity to
interact with specific cell are attached to drug carrier
nanosytems by various modifications for active
18
targeting .
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Nanoparticles target tumor sites either by ligand receptor
interaction or antigen antibody recognition3. Cell surface
antigen and receptor should have several properties that
make them ideal tumor specific targets. First, they should
express on tumor cell and not expressed on normal cells.
Second, the expression on targeted tumor cells should be
uniform. Last, cell surface antigen and receptor should
not be shed into blood circulation11. Various ligands are
used to for tumor specific targeting. Here we represent
some examples of ligands and their functions (Table-2).
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conjugate to tumor antigens via active targeting (figure
3)34.
Table 2: Ligands employed for tumor-specific targeting
and its function32
Types of Ligands
Functions
Folate
Nonimmunogenic
Folate Nanoparticles
Involved in human growth,
development, cell division and DNA
synthesis
Folate Conjugated
Nanoparticles
Used on human cervical carcinoma
cell
Transferrin
Essential role in iron homeostasis
and cell growth
Transferrin Receptor
Initiates receptor mediated
endocytosis and internalization of
transferring
Transferrin Mediated
Targeting
Enhancement of anticancer activity
Transferrin Conjugated
Nanoparticles
Enhance antitumor activity and also
contributes to the photo stability &
sustain release of drug
Vasoactive Intestinal
Peptide receptor
Angiogenesis
Polymer- Conjugated
Angiogenesis Inhibitor
TNP-470 (Caplostatin)
Inhibits hyper-permeability of tumor
blood vessels
Integrin avb3
Used targeting moiety on
nanovectors
PLGA Nanoparticles
Delivering natural products like
curcumin
Chitosan Nanoparticles
Inhibition of tumor Growth
Induction of Tumor Necrosis
Conjugation of complimentary ligands on the surface of
nanoparticles renders them to target on cancer cells.
Nanoparticles bind with receptor; they undergo receptormediated endocytosis or phagocytosis by cells resulting in
internalization of the encapsulated drugs3. For instance,
Folate targeted conjugate binds with folate receptor on
the cell surface. This complex of receptor and ligand form
endosome that is internalized by plasma membrane.
These endosomes are transferred to target cells. When
pH of endosome become acidic, lysozyme activates and
release drug from conjugate and reaches to target cells
with the help of targeting agent. Folate receptor releases
11
from the conjugate returns to the cell membrane . Liu
presented high affinity binding of quantum dot-antibody
Figure 3: Targeting strategies of nanoparticles in cancer
therapy34
Applications of Nanoparticles
Nanoparticles as Drug Carrier
Figure 4: The criteria nanoparticles need to fulfill to be
effective carriers for chemotherapeutic drugs. (a) The
nanoparticle carrier must bind or contain the desired
chemotherapeutic drug(s). (b) The nanoparticle-drug
complex must remain stable in the serum to allow for the
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Int. J. Pharm. Sci. Rev. Res., 36(2), January – February 2016; Article No. 16, Pages: 90-98
systemic delivery of the drug. (c) The nanoparticle-drug
complex must be delivered only to tumor cells. (d) The
nanoparticle must be able to release the drug once at the
site of the tumor. (e) After drug delivery, the residual
nanoparticle carrier must be safely degraded.
ISSN 0976 – 044X
generate reactive singlet oxygen species that can be used
for cancer treatment36.
Nanoparticles that serve as carriers either bind drug on
their surface or encapsulate the dug to prevent it from
degradation33. Nanoparticles have ability to penetrate
through small capillaries which allow efficient drug
accumulation at tumor sites. A sustained and controlled
release of drugs at tumor sites can be possible over a
period of days or even weeks34.
PEGylation gives stealth like characteristics to
nanoparticles, resulting in increased stability due to
inhibition of recognition by mononuclear phagocytic cell.
Nanoparticle-drug complex is targeted to tumor site
either passively or actively (figure 4)33. Cegnar have
studied that by using PLGA nanoparticles as carrier
containing cystatin, a potential anticancer drug inhibit the
tumor-associated activity of intracellular cysteine
proteases cathepsins, to limit tumor growth, and showed
that PLGA nanoparticles are useful for a rapid delivery of
protein inhibitors into tumor cells, enabling an effective
inhibition of the intracellular proteolysis34.
Additionally, conjugated polymer-drug nanotherapeutics,
such as NC-6004 [a cisplatin-incorporated PEG-poly
(glutamic acid) block copolymer micellar formulation] and
ProLindac™
(a
diaminocyclohexane-platinum
hydroxypropylmethacrylamide prodrug), are in late-stage
clinical trials35.
Nanoparticles as therapeutic agent
Photodynamic Therapy
Photodynamic therapy utilizes photosenstizers which
absorb light of certain wavelength and engender
cytotoxic oxygen based molecular species which cause
cellular damage and death by oxidative stress resulting in
apoptosis, necrosis or autophagy (Figure 5).
Currently, photodynamic therapy is being explored in the
treatment of several cancers including skin, bladder,
prostate, lung, esophageal, pancreatic, stomach and head
and neck cancer to name a few.
Figure 5: Nanoparticles in Photodynamic Therapy
Photothermal Therapy
Nanoparticles can be used in photothermal therapy to
cause localized destruction of tumors after absorption of
light due to their efficient light-to-heat conversion. The
controlled and selective heating of nanoparticles allows
thermal damage to be confined to the tumor while
minimizing any damage to surrounding normal tissue
(figure 6). 36 Nobel metal nanoparticles (such as gold
nano-spheres, nanorods and nanocages) and carbon
nanotubes show strong absorption in NIR region of
electromagnetic spectrum especially at 650 to 900 nm
due to surface Plasmon resonance. Most biological
tissues exhibit minimal light absorption in this range,
thereby allowing for increased depth penetration of
light33. Halas and coworker prepared a conjugate of HER2
antibody and gold nano-shell to target over expressing
HER2 breast carcinoma cell. In this study, it was
demonstrated that NIR irradiation causes a rise in the
temperature of the target regions of between 40 to 50ᵒ C,
which selectively destructed the carcinomas. In addition,
the survival rate of mice treated with HER-gold nanoshells and NIR irradiation was excellent compared with
37,24
the controls (non-specific antibody or NIR light alone) .
Photo sensitizers transfer energy which they absorb from
light either oxygen molecule to produce singlet oxygen or
surrounding molecules to form free radicals which
subsequently generates superoxide, hydrogen peroxide
and hydroxyl radicals. Nanoparticles used in
photodynamic therapy either act passively or actively33.
Samia prepared a conjugate of CdSe quantum dots and a
photo sensitizer, silicon phthalocyanine. In the study, it
was observed that quantum dots can sensitize
photodynamic agent either through a fluorescence
resonance energy transfer (FRET) mechanism or interact
directly with molecular oxygen through triplet energy
transfer process. Both mechanisms subsequently
Figure 6: Nanoparticles in Photothermal Therapy.
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Nanoparticles in Tumor Imaging
CONCLUSION
Various types of nanoparticles such as liposomes, dyemolecule-doped silica nanoparticles, quantum dots,
dendrimers, gold nanoparticles, immunotargeted nanoshells, per fluorocarbon nanoparticles, nano-shells, and
magnetic nano-crystals are used in molecular imaging.
Additionally,
Antibody-conjugated
paramagnetic
liposomes (diameter 300–350 nm) are used to visualize
tumor angiogenesis in vivo by magnetic resonance
imaging (MRI)34. Kobayashi and Brachbiel found that by
conjugating gadolinium to dendrimers targeting to
desired site and imaging of kidney, vascular, liver and
tumor have been successfully achieved39.
Nanotechnology has emerged as a promising technology
in the field of medicine. Nanoformulations have shown
great potential in cancer therapy not only by limiting
challenges proposed by conventional chemotherapy but
also by improving the survival rate.
Nanoparticles as Theranostic Agent
Theranostic agents are agents used simultaneously in
diagnosis and treatment. Designing of such multipurpose
nanoparticle will accelerate drug development33. Guthi
described a multifunctional methoxy-terminated PEG-bPDLLA micelle system that is encoded with a lung cancertargeting peptide (LCP) and loaded with SPIONs together
with doxorubicin for MR imaging and therapeutic
delivery, respectively. Carbon nanotubes (CNTs) have
been studied for photo acoustic and optical imaging since
they have a strong optical absorbance in the high-near
infrared region of the electromagnetic spectrum (i.e. 7001100 nm), where biological systems have a transparent
window. This therefore makes them ideal for nearinfrared photothermal ablation therapy, with the
temperature within tumors shown to increase in a lightdependent and CNT dose-dependent manner38,21.
Some nanoformulations for cancer are already in market
and some are under preclinical and clinical investigation.
Nanoparticles have already shown exciting results in
cancer therapy and holds even greater promise for cancer
patients in future.
Acknowledgement: The authors are thankful to the Head
of Department and professor of Department of
Pharmaceutical Sciences for their advice and valuable
guidance.
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Source of Support: Nil, Conflict of Interest: None.
International Journal of Pharmaceutical Sciences Review and Research
Available online at www.globalresearchonline.net
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